Zotepine

Overview

Zotepine is an atypical antipsychotic drug indicated for acute and chronic schizophrenia. It has been used in Germany since 1990 (although it has been discontinued in Germany) and Japan since 1982. WP

Zotepine is not approved for use in the United States, United Kingdom, Australia, Canada or New Zealand.[1] WP

Uses, dosage and effects

Medical uses

Zotepine's primary use is as a treatment for schizophrenia although clinical trials have been conducted (with positive results) into its efficacy as an antimanic agent in patients with acute bipolar mania. In a 2013 study in a comparison of 15 antipsychotic drugs in effectivity in treating schizophrenic symptoms, zotepine demonstrated medium-strong effectivity. Less effective than clozapine, slightly less effective than olanzapine and risperidone, approximately as effective as paliperidone, and slightly more effective than haloperidol, quetiapine, and aripiprazole.[2–6] WP

Risks and side effects

Side effects

Common[2][7] WP

• Tachycardia WP
• Hypotension WP
• Orthostatic hypotension WP
• Palpitations WP
• Hyperprolactinaemia WP
• Weight gain (produces a similar degree of weight gain to that seen with clozapine and olanzapine treatment)[6] WP
• Somnolence (2nd highest effect size for causing sedation out of fifteen antipsychotics compared in a recent meta-analysis)[6] WP
• Extrapyramidal side effects [EPSE] (2nd largest odds ratio for causing EPSE out of fifteen antipsychotics compared in a recent meta-analysis, second only to haloperidol)[6] WP
• Constipation WP
• Xerostomia (dry mouth) WP
• Blurred vision WP
• Hypersalivation (drooling) WP
• Mydriasis WP
• Anxiety WP
• Agitation WP
• Rhinitis WP
• Sexual dysfunction WP
• Dyspnoea WP
• Diarrhoea WP
• Influenza-like symptoms WP
• Cough WP
• Vertigo WP
• Confusion WP
• Dyspepsia WP
• Flushing dry skin WP
• Arthralgia WP
• Myalgia WP
• Acne WP
• Conjunctivitis WP
• Thrombocythaemia WP

Unknown frequency[2][7] WP

• QT interval prolongation WP
• Hyperthermia WP
• Hypothermia WP
• Increased serum creatinine WP
• Hyperglycaemia WP
• Hypoglycaemia WP
• Hyperlipidaemia WP
• Thirst WP
• Urinary incontinence WP

Rare[2][7] WP

• Angle-closure glaucoma WP
• Agranulocytosis WP
• Neutropaenia WP
• Eosinophilia WP
• Leukocytopenia WP
• Hypoesthesia WP
• Anaemia WP
• Myoclonus WP
• Myasthenia WP
• Alopecia WP
• Thrombocytopaenia WP
• Bradycardia WP
• Epistaxis WP
• Abdominal enlargement WP
• Deep vein thrombosis WP
• Paralytic ileus WP
• Leukopenia WP
• Tardive dyskinesia WP
• Neuroleptic malignant syndrome WP
• Laryngeal edema WP
• Urinary retention WP
• Depression WP
• Ataxia WP
• Amnesia WP
• Seizure (dose-dependent risk)[1] WP
• Metabolic syndrome WP
• Diabetes mellitus type II WP
• Cholestasis WP
• Increased liver enzymes WP
• Photosensitivity WP
• Exanthema WP
• Pruritus WP
• Hypouricemia WP
• Oedema WP

Pharmacology

Pharmacodynamics

The antipsychotic effect of zotepine is thought to be mediated through antagonist activity at dopamine and serotonin receptors. Zotepine has a high affinity for the D₁ and D₂ receptors. It also affects the 5-HT2A, 5-HT2C, 5-HT₆, and 5-HT₇ receptors. In addition, its active metabolite, norzotepine, serves as a potent norepinephrine reuptake inhibitor.[8][9] WP⚠ A table follows this text in the source and is not copied here. Open the source to see it.

Legal status

Brand names

Brand names include Losizopilon (JP), Lodopin (ID, JP), Nipolept (DE†), Setous (JP), Zoleptil (CZ, PT, TR, UK†), Zotewin (IN); where † indicates a formulation that has been discontinued. WP

Chemistry

Formula

C18H18ClNOS PC

CAS number

26615-21-4 PC

Molar mass (g/mol)

331.9 PC

IUPAC name (computed by PubChem)

2-(3-chlorobenzo[b][1]benzothiepin-5-yl)oxy-N,N-dimethylethanamine PC

SMILES

CN(C)CCOC1=CC2=CC=CC=C2SC3=C1C=C(C=C3)Cl PC

InChIKey

HDOZVRUNCMBHFH-UHFFFAOYSA-N PC

PubChem CID

5736

IUPAC name

2-(3-chlorobenzo WP

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Zotepine. 16 August 2013
2. Other British National Formulary 58. British Medical Association and Royal Pharmaceutical Society of Great Britain; 2009
3. Journal / agency Chan HY, Jou SH, Juang YY, Chang CJ, Chen JJ, Chen CH, Chiu NY. A single-blind, comparative study of zotepine versus haloperidol in combination with a mood stabilizer for patients with moderate-to-severe mania. Psychiatry and Clinical Neurosciences. April 2010. doi:10.1111/j.1440-1819.2010.02066.x · PMID 20447012
4. Journal / agency Harada T, Otsuki S. Antimanic effect of zotepine. Clinical Therapeutics. 1986. PMID 3089626
5. Journal / agency Amann B, Sterr A, Mergl R, Dittmann S, Seemüller F, Dobmeier M, Orth M, Schaefer M, Grunze H. Zotepine loading in acute and severely manic patients: a pilot study. Bipolar Disorders. October 2005. doi:10.1111/j.1399-5618.2005.00241.x · PMID 16176441
6. Journal / agency Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. September 2013. doi:10.1016/S0140-6736(13)60733-3 · PMID 23810019
7. Other Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Jun 25]. Greenwood Village, CO: Thomsen Healthcare; 2013
8. Other National Institute of Mental Health. PDSD Ki Database. 12 January 2011
9. Journal / agency Shobo M, Kondo Y, Yamada H, Mihara T, Yamamoto N, Katsuoka M, Harada K, Ni K, Matsuoka N. Norzotepine, a major metabolite of zotepine, exerts atypical antipsychotic-like and antidepressant-like actions through its potent inhibition of norepinephrine reuptake. The Journal of Pharmacology and Experimental Therapeutics. June 2010. doi:10.1124/jpet.110.166264 · PMID 20223878

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.